Fetal sex and maternal risk of pre-eclampsia/eclampsia: a systematic review and meta-analysis

Background A preponderance of male fetuses in pregnancies complicated by pre-eclampsia was described over 40 years ago. Since then, however, there has been conflicting evidence in the literature, with some studies supporting a male preponderance, some demonstrating no relationship with fetal sex, and others reporting increased risk in pregnancies bearing females. Objectives In this context, we sought to conduct a systematic review and meta-analysis to objectively evaluate the relationship between fetal sex and maternal risk of pre-eclampsia/eclampsia. Search strategy Studies from January 1950 to April 2015 were identified from PUBMED and EMBASE. Selection criteria This systematic review and meta-analysis evaluated 22 articles reporting data on fetal sex and prevalence of pre-eclampsia/eclampsia. Data collection and analysis Data were extracted by two independent reviewers. Pooled estimates of the relative risk (RR) were calculated by random-effects model. Main results Male fetus was considered the exposure and prevalence of maternal pre-eclampsia/eclampsia was the outcome of interest. We identified 534 studies through electronic searches and three studies through manual searches. Twenty-two studies fulfilled the inclusion criteria, yielding data on 3 163 735 women. Pooled analyses of these studies showed no association between male fetal sex and maternal risk of pre-eclampsia/eclampsia (RR 1.01; 95% confidence interval, 95% CI 0.97-1.05); however, a subgroup analysis including only studies that evaluated the non-Asian population (n = 2 931 771 women) demonstrated that male fetal sex was associated with increased maternal risk of pre-eclampsia/eclampsia (RR 1.05; 95% CI 1.03-1.06; I-2 = 10%; P = 0.33). Conclusion Male fetal sex is associated with maternal risk of pre-eclampsia/eclampsia in the non-Asian population.